Helicobacter pylori is an important human pathogen which causes both gastric and duodenal ulcers and has also been associated with gastric cancer and lymphoma. This microorganism has been shown to express cell surface glycoconjugates including Lewis X, Lewis Y, and sialyl Lewis X. These bacterial oligosaccharides are structurally similar to tumor-associated carbohydrate antigens found in mammals.
The presence of H. pylori isolate has been associated with an increased risk for development of gastric cancer (Wirth, H.-P., Yang, M., Karita, M., and Blaser, M. J. (1996) Infect. Immun. 64, 4598-4605). This pathogen is highly adapted to colonize human gastric mucosa and may remain in the stomach with or without causing symptoms for many years. Although H. pylori elicits local as well as systemic antibody responses, it escapes elimination by the host immune response due to its sequestered habitation within human gastric mucosa. Another mechanism by which H. pylori may protect itself from the action of the host immune response is the production of surface antigens mimicking those in the host.
In mammalian cells the enzyme fucosyltransferase (namely FucT) catalyzes the last step in the synthesis of two carbohydrate structures, Gal.beta. 1-4[Fuc.alpha.1-3] GlcNAc (Lewis X, Le.sup.x for short) or NeuAc.alpha.2-3-Gal.beta. 1-4[Fuc.alpha.1-3]GlcNAc (sialyl Lewis X, sLe.sup.x for short). (Lowe et al., 1990, Cell 57: 475-484.; Kukowska-Latallo et al., 1990, Genes & Development 4:1288-1303.) Cell surface .alpha.(1,3)- and .alpha.(1,2)-fucosylated oligosaccharides, that is, Lewis X (Le.sup.x), sialyl Lewis X (sLe.sup.x) and Lewis Y (Le.sup.y), are present on both eukaryotic and microbial cell surfaces. In mammals, Le.sup.x is a stage-specific embryonic antigen, however, Le.sup.x, sLe.sup.x and Le.sup.y are also regarded as tumor-associated markers. The biological functions of these bacterial oligosaccharide structures are not fully understood. It has been suggested that such glycoconjugates produced by H. pylori, may mimic host cell antigens and could mask the bacterium from the host immune response. It is also possible that these bacterial Lewis antigens could down regulate the host T-cell response. Therefore, production of such antigens may contribute to colonization and long-term infection of the stomach by H. pylori.
Presently, use of carbohydrates as potential therapeutic drugs has become popular in the field of medical chemistry. In addition, qualitative and quantitative carbohydrates including Le.sup.x, Le.sup.y and sLe.sup.x are also required as reagents for assaying the enzymes which are involved in the biosynthesis of glycoconjugates in cells. Le.sup.x, Le.sup.y and sLe.sup.x products which are commercially available are chemically synthesized. However, synthesis of these products gives rise to several limitations such as time-consuming, complicated procedures and low yields. Although several mammalian fucosyltransferases have been cloned and, expressed, enzymatic synthesis of Le.sup.x, Le.sup.y and sLe.sup.x products for a commercial purpose has not been reported.
The whole genome sequence of H. pylori 26695 had been published, which will undoubtedly facilitate the genetic studies of H. pylori. H. pylori genome sequence revealed the existence of two copies of .alpha.(1,3) fucT gene, whereas no putative .alpha.(1,2) fucT gene had been annotated.